For certain eye conditions and diseases, daily application of a therapeutic drug to the eye is disadvantageous and inconvenient. For these reasons, there have been many attempts to develop a device which delivers sustained release of ophthalmic drugs, is not susceptible to accidental ejection from the eye, does not cause undue discomfort to the patient receiving the drug and is a stable device which is easy to insert and remove.
Sustained delivery is accomplished in some of these devices which are extraocular inserts designed for placement inside the eyelid, external to the sclera, using tears manufactured in the eye to initiate diffusion of the drug across a membrane.
Earlier attempts at such a device include flexible ocular inserts adapted to be inserted in the conjunctival sac, the area of the eye bounded by the surfaces of the bulbar conjunctiva of the sclera and the palpebral conjunctiva of the lid. This device, known as OCUSERT.TM. is described in U.S. Pat. No. 3,828,777. This device has limitations due to varying patient tolerances which may cause retention difficulties resulting in patient pain, irritation and foreign body sensation. Problems with retention and irritation which may occur in the use of this device are documented, for example, in the following publications: P. Sihvola et al., "Practical Problems in the Use of Ocusert-Pilocarpine Delivery System", Acta Ophthalmol. (Copenh.), December 1980, 58 (6) pp. 933-937; S. E. Smith et al., "Comparison of the Pupillary, Refractive and Hypotensive Effects of Ocusert-40 and Pilocarpine Eye Drops in the Treatment of Chronic Simple Glaucoma", Br. J. Ophthalmol., April 1979, 63 (4) pp. 228-232; and I. P. Pollack et al., "The Ocusert Pilocarpine System: Advantages and Disadvantages", South Med. J., October 1976, 69 (10), pp. 1296-1298.
In an attempt to reduce patient irritation and to improve anchoring of ocular drug delivery devices outside the sclera of the eye, devices which were capable of being retained in the fornix area of the conjunctival sac were also developed. Examples of such devices include a soluble mechanism which may be inserted in the inferior fornix as described in U.S. Pat. No. 4,164,559 and OCUFIT SR.TM. (previously named "SDRD") as described in U.S. Pat. No. 5,147,647. OCUFIT SR.TM. which is inserted in the fornix, is capable of sustained delivery for 7 or more days; however, it is somewhat vulnerable to ejection from the eye due to varying levels of patient tolerance.
In an attempt to avoid problems associated with extraocular inserts, there have been several devices developed for intraocular insertion into the vitreous region of the eye.
U.S. Pat. No. 4,300,557, for example, teaches a capsule which can be filled with a pharmaceutical drug to be delivered which serves as an intraocular implant. The capsule is inserted in the vitreous region of the eye by making an incision in the eye, inserting the capsule and closing the incision. The capsule remains in place for a period of time and may be removed by making a second surgical incision into the eye and retrieving the device. The capsule has an attached tube which passes through the surface of the eye and extends outward from the eye useful for the subsequent injection of a drug. While in the vitreous, the device is not anchored and may move about freely.
A similar device has been developed for insertion in the vitreous region of the eye and is described in T. J. Smith et al., Intravitreal Sustained-Release Ganciclovir, Arch. Opthalmol., 110, 255-258 (1992) and G. E. Sanborn, et al., Sustained-Release Ganciclovir Therapy for Treatment of Cytomegalovirus Retinitis. Use of an Intravitreal Device, Arch. Opthalmol., 110, 188-195 (1992). This device contains a cup-shaped encapsulated drug for sustained delivery. The cup-shaped portion of the device contains a strut having a suture hole for suturing the device to the eye once it is inserted in the vitreous. This device, like that of U.S. Pat. No. 4,300,557, is subject to movement within the vitreous due to a lack of an effective anchoring mechanism. It also must be removed by subjecting the patient to a second operative incision.
Other related devices are disclosed in U.S. Pat. No. 5,098,443 which describes a C-shaped ring capable of being inserted in and removed from the vitreous by two separate surgical incisions and which does not contain an anchoring mechanism and U.S. Pat. No. 4,712,500 which discloses a tack-like device capable of being inserted from the retinal tissue toward the outer surface of the eye useful for the reattachment of a detached retina. This tack device does not provide a means for sustained drug delivery. At the point of insertion, there is tissue destruction which may effect a scotoma, or blind spot, in the region of the eye where the device is inserted.
Therefore, while both intraocular and extraocular devices exist which allow sustained delivery of therapeutic drugs to the eye, a need still exists for a device which is easy to position, accomplishes controlled, sustained delivery of ocular drugs preferably to the posterior regions of the eye, particularly the vitreous region, but which is not vulnerable to unwanted ejection, does not cause undue patient irritation or discomfort, is stable within the vitreous region of the eye and is removable without requiring a second full thickness incision and further intrusive eye surgery.